Tom Wade MD

Today, I review, link to, and excerpt from American Society For Reproductive Medicine‘s “Recurrent pregnancy loss: a committee opinion”. [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. Fertil Steril. 2026 Jun;125(6):1023-1041. doi: 10.1016/j.fertnstert.2026.03.001. Epub 2026 Apr 29.

All that follows is from the above resource.

The American Society for Reproductive Medicine (ASRM) defines recurrent pregnancy loss (RPL) as the spontaneous loss of two or more pregnancies, excluding confirmed molar or ectopic pregnancies. Pregnancies confirmed by urinary or blood human chorionic gonadotropin (HCG) are sufficient. Ultrasound or tissue confirmation is not required, as access to early pregnancy ultrasound and care is variable across patient populations. In addition, it has been established that biochemical pregnancy losses confer a similar impact on recurrence risk as clinical losses, supporting the inclusion of biochemical pregnancy losses in the definition of RPL (1–3). Recurrent pregnancy loss is a disease distinct from infertility, requiring its own specific evaluation and management. There are inconsistent definitions of miscarriage (or spontaneous abortion) in the literature to define pregnancy losses as less than 20 or 22 weeks. For the purpose of this document, we will use less than 22 weeks, which is consistent with the International Glossary of Infertility and Fertility Care (4). Pregnancy loss after 22 weeks is considered a stillbirth or fetal demise and is outside the scope of this document and covered by a dedicated American College of Obstetricians and Gynecologists (ACOG)/Society for Maternal-Fetal Medicine consensus guideline (5, 6).

Approximately 50%–60% of first-trimester miscarriages are due to embryonic aneuploidy (7). Sporadic aneuploidy is strongly correlated with maternal age. Aneuploidy plays a smaller role in second and third trimester losses and stillbirths, impacting 20% of stillborn fetuses at 22 weeks of gestation, 6% of stillborn infants at term, and 0.1%–5% of term live births (8). When compared with individuals with isolated miscarriage, patients with RPL have a higher likelihood of euploid miscarriage. The likelihood of euploid miscarriage further increases with the number of miscarriages. Large observational cohort studies show that women with RPL have an elevated risk of several serious health conditions later in life, including cardiovascular disease, stroke, diabetes, autoimmune disorders, and mental health disorders (9). Therefore, a complete evaluation of maternal and paternal health is essential in the setting of recurrent miscarriage, especially if ≥ 1 miscarriages are found to be euploid, termed ‟unexplained’’. The definition of RPL does not require miscarriages to be consecutive, due to a lack of definitive associations with consecutive miscarriages and known risk factors for RPL. However, clinicians are urged to use their judgment on when to initiate a partial or complete workup in the setting of nonconsecutive miscarriages, as limited data indicate that consecutive miscarriages have a poorer prognosis for live birth than nonconsecutive miscarriages in one observational cohort (10). Management of this traumatic diagnosis drives patients and providers to seek answers and attempt unproven therapies. However, counseling about the natural history of RPL is a key component and responsibility of the provider, as 50%–80% of patients will succeed in their subsequent pregnancy attempt with no specific interventions (11, 12). Although ASRM supports shared decision-making in the absence of high-quality data, taking care of patients with this multifactorial disorder should include an evidence-based approach in a supportive environment to minimize risks of harm because of unproven treatments.

In this document, we present a stepwise algorithm for the evaluation of RPL, with the recommendation to perform chromosome evaluation of the miscarriage, followed by additional testing as indicated (see Fig. 1, Table 1, and Table 2). The incremental benefit of adding miscarriage testing to the diagnostic workup of patients with recurrent miscarriage has been demonstrated in numerous studies (13–15).

Therefore, we propose a stepwise algorithm, which provides more explanations and substantial cost savings by avoiding unnecessary testing when miscarriages are explained. Although chromosome testing at the time of first miscarriage can be offered for explanatory purposes, a single euploid early miscarriage has not been shown to increase the risk of second loss (16); therefore, reflex testing for other causes of losses is not indicated after a single euploid miscarriage.

Table 1. Testing in couples/ individuals identified with recurrent pregnancy loss.

 

Evaluation		Indication	Test
Recommended
	Chromosome evaluation of miscarriage tissue	All patients	Array-based chromosome testing
	Uterine cavity evaluation	All patients	HSG, saline sonogram, or hysteroscopy
Recommended in certain circumstances
	Parental karyotypes	Miscarriage with unbalanced translocation or no miscarriage testing	Blood karyotype of male and female
	Antiphospholipid antibodies	Clinical criteria for antiphospholipid syndrome (APS) – 3 or more consecutive losses – personal history of thrombosis	Anticardiolipin IgG and IgM Beta-2-glycoprotein IgG and IgM Lupus anticoagulant
	Thyroid	Risk factors or symptoms, Euploid miscarriage, or no miscarriage testing	TSH
	Chronic endometritis	Recurrent unexplained miscarriage or concurrent infertility	Endometrial biopsy with CD138 staining
	Sperm DNA fragmentation testing	Recurrent unexplained miscarriage or concurrent infertility	Sperm DNA fragmentation Reproductive urology evaluation
	Diabetes	Risk factors or symptoms (PCOS, obesity, age >40)	HgbA1c
	Prolactin	Symptoms of hyperprolactinemia (anovulation, galactorrhea)	Fasting prolactin
Not recommended
	Inherited thrombophilia	Not recommended	Factor V Leiden, Prothrombin gene, MTHFR, protein C, protein S, antithrombin 3, homocysteine
	Autoimmune testing outside of APS	Not recommended	Thyroid antibodies
	Endometrial receptivity testing	Not recommended	NK cell testing
	Microbiome testing (including mycoplasma and ureaplasma)	Not recommended
Note: APS = antiphospholipid syndrome; DNA = deoxyribonucleic acid; HSG = hysterosalpingography; IgG = immunoglobulin G; IgM = immunoglobulin M; MTHFR = methylenetetrahydrofolate reductase; NK = natural killer; PCOS = polycystic ovary syndrome; TSH = thyroid-stimulating hormone. American Society for Reproductive Medicine Practice Committee. Recurrent pregnancy loss. Fertil Steril 2026.

Table 2. Treating couples/individuals identified with recurrent pregnancy loss.

Treating couples/individuals identified with recurrent pregnancy loss
Standard recommended treatments	✔ Preconception optimization of maternal health conditions (such as lupus, hypertension) ✔ Psychological support ✔ Treatment of APS with heparin and low-dose aspirin ✔ Treatment of overt thyroid disease ✔ Treatment of uncontrolled Diabetes Mellitus ✔ Genetic counseling in a setting of known genetic cause (parental translocation) or high-risk family history ✔ Treatment of hyperprolactinemia
Treatments of possible benefit, with limited or conflicting studies	✔ Correction of uterine cavity abnormalities (uterine septum, polyps, submucosal fibroids, intrauterine adhesions) ✔ Addition of progesterone support if the patient has bleeding in the first trimester ✔ Empiric use of progesterone in the luteal phase ✔ Treatment of chronic endometritis ✔ Reproductive Urology evaluation if elevated sperm DNA fragmentation ✔ Use of Metformin for women with PCOS or evidence of insulin resistance ✔ IVF for PGT-A or PGT-SR ✔ Use of donor gametes in a setting of genetic cause found or advanced maternal age with diminished ovarian reserve
Treatments proven ineffective or no evidence of benefit	✔ Use of empiric aspirin and thrombolytics in the absence of positive APS testing ✔ Treatment of endometriosis and adenomyosis ✔ Treatment of hyperprolactinemia in the absence of ovulatory disorder ✔ Treatment of inherited thrombophilia ✔ Thyroid hormone supplementation in patients with isolated TPO antibodies or TSH less than 4 mIU/L ✔ IVIG, intralipids, or prednisone
Note: APS = antiphospholipid syndrome; DNA = deoxyribonucleic acid; IVIG = intravenous immunoglobulin; IVF = in vitro fertilization; PCOS = polycystic ovary syndrome; PGT-A = preimplantation genetic testing for aneuploidy; PGT-SR = preimplantation genetic testing for structural rearrangements; TPO = thyroid peroxidase; TSH = thyroid-stimulating hormone. American Society for Reproductive Medicine Practice Committee. Recurrent pregnancy loss. Fertil Steril 2026.

SUMMARY

The following statements address specific aspects of testing and treating couples or individuals with RPL:

• ASRM defines recurrent pregnancy loss (RPL) as the spontaneous loss of two or more pregnancies, excluding confirmed molar or ectopic pregnancies. Pregnancies confirmed by urinary or blood HCG are sufficient.
• ASRM recommends chromosome analysis of miscarriage tissue, when feasible, as a first step in the evaluation of the couple with RPL. ASRM joins ESHRE and ACOG in recommending array-based technology for analysis of miscarriage tissue on the basis of its many technical advantages over traditional cytogenetic analysis. Options for at-home collection of tissue for miscarriage tissue testing should be discussed with patients at the time of miscarriage for patients who do not desire surgical management.
• A uterine cavity evaluation should be offered to all women with unexplained RPL and can be considered in patients with aneuploid miscarriages to evaluate for anatomic abnormalities that could lead to miscarriage or sequelae from prior miscarriages, such as adhesions and retained pregnancy tissue. It is reasonable to offer surgical treatment of a uterine septum and acquired uterine defects, including endometrial polyps, submucosal fibroids, retained pregnancy tissue, and intrauterine adhesions, in women with RPL.
• Screening for parental balanced structural chromosomal rearrangements should be offered when an unbalanced structural chromosome rearrangement is detected in miscarriage testing or when no chromosomal testing of miscarriages is available. Additional studies are warranted to determine the overall effectiveness of PGT-SR in the setting of parental chromosome rearrangements.
• A laboratory evaluation for antiphospholipid antibodies is recommended for individuals who meet clinical criteria for antiphospholipid antibody syndrome. Treatment should include a low-dose aspirin before conception or with initiation of prophylactic heparin at the time of clinical or laboratory evidence of a pregnancy.
• Women with RPL who have had euploid miscarriage or no testing of miscarriage tissue should be screened for hypothyroidism with measurement of TSH and treated if TSH >4 mIU/L or the upper limit of normal in the laboratory. Given the high-quality data demonstrating no benefit of treating euthyroid women with thyroid autoimmunity, we do not recommend screening for thyroid antibodies.
• Until recently, limited data existed to inform best practice, and some evidence suggested a benefit to screening and treating endometritis. However, a recent high-quality RCT presented as an abstract demonstrated no benefit of prescribing doxycycline for chronic endometritis in RPL patients.
• Sperm DNA fragmentation testing may be considered in patients with otherwise unexplained recurrent miscarriage or RPL and concomitant infertility. Further research is necessary to determine if treatment improves pregnancy outcomes.
• Given the association of uncontrolled DM with pregnancy complications and the need for glycemic control before conception to optimize outcomes, ASRM recommends measuring an HbA1C during the diagnostic workup of women with RPL if risk factors are present. Risk factors for DM include being overweight or obese (i.e., high BMI), family history of DM, age >40, PCOS, and history of gestational diabetes.
• Although the evidence of benefit in the setting of RPL is indirect, it is reasonable to consider metformin in women with PCOS, with evidence of insulin resistance and otherwise unexplained miscarriage. Further studies are needed to clarify the optimal patient population, dosage, and timing of initiation and discontinuation before definitive recommendations can be made.
• Prolactin testing is not recommended in women with RPL, except in the evaluation of coexisting clinical symptoms, such as galactorrhea or anovulation.
• Additional prospective clinical trials are needed to determine if progesterone supplementation in women with RPL can improve live birth rates. Vaginal progesterone may be offered in early pregnancy in the setting of vaginal bleeding and/or recurrent unexplained miscarriage using a shared decision-making model.
• Overall, PGT-A has not been shown to significantly reduce miscarriage or improve live births compared with EM in the setting of RPL. In women over 40 years with a proven aneuploid miscarriage, it is reasonable to discuss PGT-A using a shared decision-making model to reduce miscarriage because of aneuploidy. However, patients should be counseled that PGT-A has not been shown to reduce the time to successful pregnancy or increase live birth rate compared with EM. Prospective clinical trials in patients with RPL are needed.
• Routine testing for thrombophilias is not recommended among women with RPL. The use of anticoagulants for the treatment of RPL with hereditary thrombophilias or unexplained RPL is not recommended, on the basis of high-quality evidence showing no benefit on livebirth or miscarriage rate.
• ASRM does not recommend routine testing for ovarian reserve in the evaluation of RPL because the association between RPL and ovarian reserve is unclear and no effective therapeutic interventions exist.
• ASRM does not recommend routine immune testing and treatment in the evaluation of RPL.
• Although the data on lifestyle interventions on miscarriage risk are limited, given the known risk of certain exposures in pregnancy and the possible impact on miscarriage risk, these exposures should be reduced whenever possible preconception. Smoking cessation is strongly recommended.
• The RPL couples are at risk for psychological sequelae. Psychological support is an essential part of miscarriage care and should be offered to all couples experiencing miscarriage and planning future pregnancy

CONCLUSIONS

RPL is identified in a woman with the loss of two or more presumed intrauterine pregnancies before 22 completed weeks of pregnancy. An algorithm is presented that guides the diagnostic workup on the basis of the chromosome status of the second miscarriage, while still allowing for provider judgment for higher numbers of miscarriages or untested miscarriages.

In this updated Committee Opinion, etiologies and treatments for RPL are presented in the context of the latest research advances in the field. One of the biggest challenges of treating patients with unexplained recurrent miscarriage is the high percentage of patients who remain unexplained if chromosome testing of the miscarriage is not performed, which can compel patients to request unproven diagnostic tests and therapies. Although ASRM supports shared decision-making, counseling patients with this multifactorial disorder should include an evidence-based approach in a supportive environment to minimize risks of unproven treatments. Expectant management should be discussed as a viable option, as the success rate is 50%–80% for the majority of patients with unexplained RPL (11, 174). As researchers and providers, it is essential that we continue to work to find patients’ answers and effective treatments and to continue to critically evaluate the literature as it emerges. Further research is needed in several areas, such as genetic and immune predisposition to miscarriage, endometrial factors, and therapies to mitigate the psychological impact of miscarriage on families. Empiric use of other treatment modalities has been suggested for unexplained RPL. However, studies have not shown benefit to RPL patients with routine use of low-dose aspirin, enoxaparin, glucocorticoids, heparin, endometrial scratching, granulocytecolony stimulating factor (G-CSF), intralipid therapy, routine use vaginal progesterone, alloimmune causes, or treatment with intravenous immunoglobulin (IVIG), or lymphocyte immunization therapy. At the present time, the use of empiric thrombolytics is not recommended for unexplained RPL.